Alcoholism is the addiction to or dependency upon drinking excessive amounts of alcoholic beverages such as beer, wine and distilled spirits. Alcoholism is sometimes also referred to as alcohol abuse or alcohol dependence.
The biological mechanisms underpinning alcoholism are uncertain, however risk factors include stress, mental health problems, and genetic predisposition. Long-term alcohol abuse produces physiological changes in the brain that result in alcohol withdrawal syndrome upon discontinuation of alcohol consumption. Alcohol damages almost every organ in the body, and the alcoholic risks suffering medical and psychiatric disorders.
Treatment of alcoholism is problematic and typically includes alcohol detoxification to withdraw the alcoholic person from drinking alcohol. Neurologically active drugs, such as benzodiazepines, may be used to manage alcohol withdrawal symptoms. Post-medical care, such as psychological therapy, is usually required to maintain alcoholic abstention.
Disulfuram is a drug that causes an acute sensitivity to ingested alcohol (ethanol), and is sometimes used in the treatment of chronic alcoholism. Alcohol is broken down in the liver by the enzyme alcohol dehydrogenase to acetaldehyde, which is then converted by the enzyme acetaldehyde dehydrogenase to acetic acid. Disulfuram blocks the enzyme acetaldehyde dehydrogenase. Thus, disulfuram can cause the concentration of acetaldehyde in the blood of a human being who has consumed alcohol to be substantially higher (e.g., 5 to 10 times higher) than that found in the blood of a person who consumed the same amount of alcohol in the absence of disulfuram. Acetaldehyde is one of the major causes of the symptoms of a “hangover”, and so consumption of disulfuram produces severe negative reaction to alcohol. Symptoms include flushing of the skin, accelerated heart rate, shortness of breath, nausea, vomiting, throbbing headache, visual disturbance, mental confusion, postural fainting, and circulatory collapse.
Disulfuram has clinical limitations, however, due to poor compliance by patients, and a range of side-effects, such as drowsiness, headache and, less often, neurotoxicity. Disulfuram is usually administered daily in order to be effective, and so it is easy for a patient to discontinue use of the drug.
Thus, there is a continuing need for compositions and methods for suppressing, reducing and/or eliminating the activity of the acetaldehyde dehydrogenase that is involved in metabolising alcohol in a mammal, particularly a human being. Such compositions and methods can be used, for example, in the treatment of alcoholism. In particular, there is a need for compositions and methods that suppress, reduce and/or eliminate the activity of acetaldehyde dehydrogenase for a period of time (e.g., weeks or months) that is significantly longer than the effective period of disulfuram, thereby making it difficult for a human subject to discontinue alcohol aversion therapy after consuming such a relatively long lasting inhibitor of ALDH. There is also a particular need for compositions and methods that suppress, reduce and/or eliminate the activity of acetaldehyde dehydrogenase and that have fewer, or less severe, side effects than disulfuram.